DESCRIPTION (Verbatim from Applicant's Abstract):The overall objective of this program is to validate Sedum's new Bi-AcervateTM nanoparticle formulation for delivery of drugs, proteins and DNA. One of the current challenges in drug development today is efficient delivery of chemical and biological medicines. Microparticle and encapsulation techniques that stabilize bioactive ingredients and minimize systemic toxicity often are difficult and expensive to produce at large scale. Sedum Laboratories, Inc. has developed a novel encapsulation method based on coacervation of two oppositely charged biocompatible polymers with a charged drug or macromolecule. Bi-AcervateTM nanoparticles incorporate drugs and macromolecules with high efficiency and release them slowly in vivo. Sedum now proposes to validate this technology by optimizing the formulation to maximize incorporation efficiency, stability and safety of amphotericin B. Amphotericin B is the only drug effective against severe systemic fungal infections in immunocompromised patients, but its use is limited by severe toxicity. Liposomal preparations are so expensive that they are not used routinely in some medical centers. Candidate BiAcervate formulations will be evaluated for cytotoxicity and anti-fungal activity in vitro and in an experimental model of systemic fungal infection in mice. PROPOSED COMMERCIAL APPLICATION: Sedum proposes to enter the $14B market for advanced drug delivery systems by developing a new nanoparticle formulation of Amphotericin B. This will have a greater therapeutic index and fewer toxic side effects than conventional drugs, and will be easier and less costly to produce than liposomal forms. Amphotericin B is the most effective drug for treating severe systemic fungal infections, which afflict 100,000 immunocompromised patients a year.